Table 8.
Drugs for treatment of PAH
| Drugs | Target | Action Mechanisms | References |
|---|---|---|---|
| Membrane receptor agonist or antagonist | |||
| Epoprostenal/PGI2 (Flolan, Veletri) | ↑ Prostacyclin receptor (IP) | Induces vasodilative, antiproliferative and anticoagulant effect by IP-mediated increase in cAMP and PKA | (24, 32, 84, 609) |
| Treprostinil (Remodulin, Tyvaso) | ↑ IP receptor | Activates IP to induce pulmonary vasodilation and inhibit pulmonary vascular remodeling | (610, 611) |
| Iloprost (Ventavis) | ↑ IP receptor | Activates IP to induce pulmonary vasodilation and attenuate pulmonary vascular remodeling | (612, 613) |
| Selexipag (Uptravi) | ↑ IP receptor | Activates IP to induce pulmonary vasodilation and attenuate pulmonary vascular remodeling | (614, 615) |
| Bosentan (Tracleer) | ↓ Endothelin receptor A (ETA), ↓ endothelin receptor B (ETB) | Blocks both ETA and ETB to inhibit vasoconstriction and vascular remodeling by inhibiting PASMC contraction and proliferation | (90, 156, 243, 605, 616, 617) |
| Ambrisentan (Letairis) | ↓ETA | Selectively blocks ETA to inhibit vasoconstriction and vascular remodeling | (618, 619) |
| Macitentan (Opsumit) | ↓ETA and ↓ETB | Blocks both ETA and ETB to inhibit vasoconstriction and vascular remodeling | (620, 621) |
| Imatinib | Platelet-derived growth factor receptor (PDGFR) | Nonselective blocker of tyrosine kinase receptors to inhibit cell proliferation and concentric pulmonary vascular remodeling | (245, 622, 623) |
| Sotatercept | Activin receptor type 2A (ACTRIIA or ACVR2A) | A recombinant ACTRIIA extracellular domain fused with IgG-Fc domain to neutralize activin proteins and GDF-8 (myostatin) and GDF-11 (BMP11), which then blocks the activin and GDF ligands and indirectly restores or enhances BMP signaling | (624, 625) |
| Ion channel and transporter inhibitor or activator | |||
| Diltiazem | ↓Voltage-dependent Ca2+ channel (VDCC) | Inhibits Ca2+ influx, decreases [Ca2+]cyt in PASMCs and attenuates pulmonary vasoconstriction or induces pulmonary vasodilation | (626, 627) |
| Nifedipine | ↓ L-type VDCC | Inhibits Ca2+ and Na+ influx in cardiomyocytes and vascular smooth muscle cells to inhibit pulmonary vasodilation and induce pulmonary vasodilation | |
| Verapamil | ↓VDCC | Inhibits Ca2+ influx and decreases [Ca2+]cyt in PASMCs to attenuate pulmonary vasoconstriction and induce pulmonary vasodilation | |
| Amlodipine | ↓VDCC | Inhibits Ca2+ influx, decreases [Ca2+]cyt in PASMC, and causes pulmonary vasoconstriction or induces pulmonary vasodilation | |
| Digoxin (Lanoxin) | ↓Na+-K+-ATPase | Exerts positive ionotropic effect to improve RV function and inhibits hypoxia-inducible factor (HIF)-1α to attenuate vasoconstriction and vascular remodeling | (628, 629) |
| Nitric oxide (NO)/cGMP signaling stimulator | |||
| Inhaled NO | ↓ Soluble guanylate cyclase (sGC) | Activates sGC to produce cGMP and induce vasodilation by activating K+ channels and inducing membrane hyperpolarization | (85, 144, 430, 630, 631) |
| Riociguat (Adempas) | ↓ sGC | Stimulates sGC to produce cGMP and induce vasodilation and regression of vascular remodeling | (632–636) |
| Tadalafil (Adcirca) | ↓ Phosphodiesterase 5 (PDE-5) | Inhibits PDE-5 to decrease cGMP degradation and induce cGMP/PKG-mediated vasodilation and regression of vascular remodeling | (637–639) |
| Sildenafil (Revatio) | ↓ PDE-5 | Inhibits PDE-5 to decrease cGMP degradation and induce cGMP/PKG-mediated vasodilation and regression of vascular remodeling | (640, 641) |
| Anticoagulant | |||
| Warfarin (Coumadin) | Vitamin K epoxide reductase | Blocks vitamin K epoxide reductase to inhibit coagulation | (642–644) |
| Other | |||
| Oxygen (O2) | Inhalation of O2 inhibits hypoxic pulmonary vasoconstriction, improves gas exchange,. and increases arterial oxygenation | ||
↑, Increase, activate; ↓, decrease, inhibit. [Ca2+]cyt, cytosolic free Ca2+ concentration; PAH, pulmonary arterial hypertension; PASMC, pulmonary arterial smooth muscle cell; RV, right ventricle.